It is the objective of this proposal to initiate a study of the role of Fibroblast Growth Factors in regeneration of the eye lens in the amphibian, Notophthalmus viridescens, the Eastern Spotted Newt. The adult newt is unique in this ability to regenerate in vivo an eyes lens from the dorsal iris epithelium after lensectomy. The restriction in vivo for lens regeneration to the dorsal iris epithelial cells, together with this tissue's shorter cell cycle time (compared to ventral iris epithelium) after re-entry into cell cycle, suggests that the capacity for lens regeneration may be related to mitogenic activity. It has long been known that a factor, emanating from the neural retina, is necessary for lens regeneration in vivo. Preliminary experiments by the P.I., with an exogenous mitogenetic, neural retina-derived, growth factor containing Fibroblast Growth Factors, indicate a role in directing (non- regenerating) ventral iris in vivo to regenerate lens. Microinjection and/or instillation of implants of purified FGF's into lentectomized and lentectomized/dorsal Iris-removed adult newt eyes, accompanied by 3H thymidine autoradiography of iris tissue; analysis of possible differential (dorsal versus ventral iris) FGF receptor distribution and occupancy using for 125I FGF's; immunohistochemical analysis of aFGF, bFGF, and FGF receptor localization with specific antibodies; and aFGF, bFGF, and FGF-receptor mRNA localization, using in situ hybridization with 35S and/or digoxigenin riboprobes will establish the temporal and spatial distribution of these growth factor entitles, and any causal relationship to evocation of lens regeneration. The sequence of cellular events and growth factor involvement leading to in vivo lens regeneration results in perhaps the clearest example of true transdifferentiation in developmental biology today. Additional knowledge of the factor involved in initiation of lens regeneration in this organism, may lead to future application and advances in eyes lens replacement in mammals, including man.